INTRODUCTION: Hereditary hemochromatosis is an autosomal recessive disorder of iron absorption, leading to organ dysfunction. C282Y gene homozygosity is implicated in 80%–95% of cases of hereditary hemochromatosis. The clinical penetrance of this genotype remains unclear. The purpose of the study was to better describe the clinical penetrance and disease progression of C282Y homozygotes. METHODS: This is a retrospective study of all individuals in Newfoundland and Labrador, Canada, homozygous for the C282Y mutation from 1999 to 2009. Using electronic health records, laboratory values, phlebotomy status, radiologic reports, and clinic records were recorded up to November 2017. Iron overload status was classified via the HealthIron study. SPSS Version 19.0 (IBM Corporation) was used for descriptive statistics. Predictors of disease penetrance were assessed with logistic regression; a Student t test was used for continuous variables, and χ 2 tests were used for categorical variables. RESULTS: Between 1999 and 2009, 360 individuals tested positive for C282Y/C282Y. The mean age of diagnosis was 49.1 years. Three hundred six individuals had adequate follow-up for analysis (mean 11.6 years). End-organ damage was observed in 18.3%, with 5.8% developing liver disease. End-organ damage was more frequently observed in men 24.3% vs 10.5% ( P < 0.05). Clinical penetrance in postmenopausal women approached that of men 18.3%. DISCUSSION: This is the largest reported cohort of C282Y homozygotes, followed for an extended duration of time in North America. The findings reflect outcomes in routine clinical practice and suggest that C282Y homozygosity uncommonly causes end-organ damage and liver disease.
Primary outcome was the incidence of PEP. The diagnosis and severity of PEP were defined by the ASGE lexicon for endoscopic adverse events. Patient-related factors, operator-related factors, procedure-related factors and preventive measures were accumulated. The risk factors and preventive measures for PEP were examined by using univariate and multivariate analyses. Results: A total of 16,032 ERCP procedures were performed in the 36 centers during the period, 3,739 ERCPs were enrolled in this study. The average of age was 72.5 years and 43.7% of patients were women. PEP developed in 258 cases (6.9%); 201 mild, 39 moderate, 17 severe, and 1 fatal. Multivariate analysis was performed using 20 risk factors and 8 preventive measures. On multivariate analysis, the significant factors were women under 50 years old, ASA-PS 3, normal serum bilirubin level, obstruction of main pancreatic duct at the pancreatic head, guidewire insertion for the pancreatic duct, total procedure time >60 minutes, prophylactic pancreatic stenting, rectal administration of NSAIDs after ERCP, and spraying saline-epinephrine (Table 1, 2). Conclusions: The extracted risk factors for PEP were young women, normal serum bilirubin level, guidewire insertion for pancreatic duct and prolonged procedure time. Prophylactic pancreatic stenting and spraying saline-epinephrine were suggested to be effective as preventive measures for PEP. The administration of NSAIDs after ERCP was considered a risk factor rather than a preventive measure. However, since the operators decided to administer NSAIDs based on the patient conditions during and after the procedures, then we have to consider what factors were hidden behind the post-ERCP NSAIDs administration.
Background We describe an unusual case of NSAID-induced gastric outlet obstruction (GOO) in the absence of malignancy or ulcers. This was successfully managed conservatively with drug withdrawal and serial endoscopic balloon dilation (EBD). Aims Case Report Methods Case Report and Literature Review Results A 58-year-old woman with 20-year history of daily Ketorolac use for osteoarthritis presented with iron deficiency anemia (IDA) of 58 g/L and post-prandial emesis for 2 months. There was no overt GI bleeding. Gastroscopy revealed severe erosive esophagitis and GOO with no ulcers. After a negative CT imaging ruled out extrinsic malignant compression, GOO was managed with EBD. Examination of the duodenum post-EBD revealed complete atrophy and scalloping. Focused biopsies reveal chronic gastritis, complete villous atrophy in the duodenum; ruled out H. Pylori, celiac disease, amyloidosis and dysplasia. EUS negative for infiltrative disease or regional adenopathy. Vitamin B12, anti-TTG I IgA, HLA DQ2/8 were normal. These findings made drug-induced enteropathy the top contender. PPI therapy was initiated and NSAID discontinued. Five serial EBD were performed over 4 months to 18mm. A pureed diet was tolerated after 2 dilations. Follow-up at 3 months showed partial recovery of enteropathy and pyloric stenosis. No adverse events were seen. The severe esophagitis was likely an erosive process secondary to reflux from GOO. Her IDA is likely multifactorial: Severe enteropathy and GOO may have led to chronic malabsorption; occult GI bleeding from erosions or ulcers that have healed may further contribute. Ketorolac could explain the enteropathy. COX-1 inhibition leads to decreased gastric cytoprotection. In rat models, COX-2 inhibition has been suggested to delay gastric healing and dysregulated immune response to food antigens in the small bowel [4–6]. NSAID-induced GOO almost always occur in the context of peptic ulcer disease [1,2]. A similar case [3] found pyloric stenosis in a 75-year old woman with esophagitis and ulcer-induced pyloric stenosis. They postulate that post ulcerative healing led to benign pyloric stenosis and explained the absence of ulcers. Historically, surgical intervention and stent placement have played a major role in the management of benign mechanical GOO. EBD has replaced surgical intervention as first line therapy [7] showing promising results beyond 3 months post EBD[8], sparing patients from surgery related morbidity. An algorithm has been suggested by us [Img 1] for the management of benign GOO. Conclusions We present an unusual case of NSAID-induced mechanical GOO and enteropathy. This case highlights these entities as rare but serious complications of chronic NSAID use. Management of benign mechanical GOO should be individualized. Prudence with prescribing NSAIDs to at risk populations is recommended. Funding Agencies None
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.